Despite the growing sophistication of medical technology, repairing and replacing damaged tissues remains a costly, and serious problem in health care. Currently, implantable prostheses for repairing tissues are made from a wide number of synthetic and natural materials. Ideally, these prosthetic material should be chemically inert, biocompatible, noncarcinogenic, capable of being secured at the desired site, suitably strong to resist mechanical stress, capable of being fabricated in large quantities in the form required, sterilizable, and free of viruses or other contaminating agents. Examples of tissue that can be treated with implantable prostheses include dura mater, tendon (e.g., rotator cuff, anterior cruciate, etc.) and rectic abdominus muscle due to herniation.
A wide variety of prosthetic materials have been used, including tantalum, stainless steel, Dacron, nylon, polypropylene (e.g., Marlex), microporous expanded-polytetrafluoroethylene (e.g., Gore-Tex), dacron reinforced silicone rubber (e.g., Silastic), polyglactin 910 (e.g., Vicryl), polyester (e.g., Mersilene), polyglycolic add (e.g., Dexon), and cross-linked bovine pericardium (e.g., Peri-Guard). To date, no single prosthetic material has gained universal acceptance.
Metallic meshes, for example, are generally inert and resistant to infection, but they are permanent, do not generally adapt in shape as a skeletal structure grows, and they shield the healing tissues from the stresses that may be necessary to generate fully functioning tissue. Non-resorbable synthetic meshes have the advantage of being easily molded and, except for nylon, retain their tensile strength in the body. Their major disadvantages are their lack of inertness to infection, the occasional interference with wound healing, and that they are often long-term implants. Absorbable meshes have the advantage of facilitating tissue in-growth and remodeling at the site of implantation, but often do not have the short-term or long-term mechanical strength necessary for the application.
Both U.S. Pat. No. 4,948,540, granted to Nigam and U.S. Pat. No. 5,206,028 granted to Li, disclose a collagen membrane suitable for medical uses. In the case of Li, the membrane is constructed in a fashion to make it easier for implantation, by ensuring the membrane is not transparent, and not slippery. Both patents begin by providing a solution of collagen, which is freeze-dried, cross-linked, and then compressed. Li then utilizes a second cross-linking, freeze-drying and compression step. The initial cross-linking step locks the fibers into a specific orientation. The compression step merely reduces the porosity within the sheet without inducing fiber migration that would substantially improve the strength of the composition. A second cross-linking step is necessary to hold the sheet in its compressed conformation. What is needed is a sheet with improved strength, capable of maintaining its structural competence without the need of multiple freeze-drying and cross-linking steps.
In U.S. Pat. No. 6,599,524 granted to Li, there is disclosed a membrane sheet having oriented biopolymeric fibers. The membrane is manufactured with oriented parallel fibers formed around a rotating mandrel. The rotations of the mandrel as the fibers are added results in the orientation of the fibers. The membrane is then compressed to drive out excess liquid, and cross-linked, resulting in a membrane with directionally oriented fibers. This material is only aligned in a single direction and must be laminated with binding agents in order to create a functional device. Additionally, such a device does not provide gradients such as those seen in natural tissues. What is needed is a method that allows for layering that occurs at the microscopic as well as the macroscopic level as part of a one step process and more closely represents the layered structure of natural connective tissues.
Prosthetic devices are used in the repair, augmentation, or replacement of articulating organs. For example, the rotator cuff (i.e., shoulder joint) is made up by a combination of the distal tendinous portion of four muscles: the supraspinatus, subspinatus, subscapularis and the teres minor. Proper functioning of this tendonous cuff, depends on the fundamental centering and stabilizing role of the humeral head with respect to sliding action during lifting and rotation movements of the arm. A tear in the rotator cuff tendons is a common injury that can be caused by constant friction from repetitive overhead motion, trauma, or age-related degeneration that can narrow the space between the clavicle and the top of the scapula.
To repair large tears of the rotator cuff, it is desirable to use a scaffold or graft material to help support the damaged tissue and guide its repair. Several types of materials have been used for such procedures. Wright Medical (Memphis, Tenn.) markets a product known as GraftJacket, which is manufactured by Lifecell Corporation (Branchburg, N.J.) from human cadaver skin. Human cadaverous tissue products can be difficult to obtain and have the potential for disease transmission. Tissue Sciences (Covington, Ga.) markets a product known as Permacol, which is comprised of cross-linked porcine dermis. DePuy (Warsaw, Ind.) markets the Restore Patch which is fabricated from porcine small intestine submucosa. Biomet (Warsaw, Ind.) markets a product known as CuffPatch another porcine small intestine product. The CuffPatch and the Restore Patch products provide biocompatible scaffolds for wound repair but they are complicated to manufacture, as they require the lamination of multiple layers of submucosal tissues to gain the strength needed for these applications. Fabrication of such patches from porcine small intestine submucosa are described in U.S. Pat. No. 4,902,508 Badylak et al. and U.S. Pat. No. 5,573,784 Badylak et al.
Additional applications for prosthetic devices exist in the form of membrane patches. The spinal cord and brain are covered with a protective membrane that is known as the dura mater. The integrity of the dura mater is critical to the normal operation of the central nervous system. When this integrity is intentionally or accidentally compromised (e.g., ruptured, severed, damaged, etc.), serious consequences may ensue, unless the membrane can be repaired. Typically, dura tissue is slow to heal. To enhance the healing process, graft materials can be utilized to guide the regeneration of the tissue. Repairing damaged membranes has largely focused on implantable materials known as dural substitutes, which are grafted over the damaged dura mater and are designed to replace and/or regenerate the damaged tissue.
Thus, there is a need for an effective dura substitute that would be biocompatible, sufficiently noninfectious (e.g., purified, etc.) to prevent the transmission of disease, conformable, available in a variety of sizes, high in tensile strength, inert, suturable, and optionally capable of forming a water-tight seal.
Researchers have experimented with a wide variety of substances to act as dura substitutes. Autologous grafts of tissue, such as pericardium, can be effective as a dura substitutes; however, autologous tissue is not always available and it posses additional costs and risks for the patient. Cadaverous dura mater has also been used but like autologous tissues, cadaverous tissues can be difficult to obtain. Tutogen Medical Inc. (West Paterson, N.J.) markets a product known as Tutoplast dura mater, which is obtained from human cadavers. Processed human cadaveric dura mater has been implicated in the transmission of cases of the fatal Creutzfeldt-Jakob disease. Other products overcome this shortcoming by using alternate materials. The Preclude Dura substitute, manufactured by W. L. Gore (Newark, Del.), is an inert elastomeric fluoropolymer material. The material is biocompatible but is a permanent implant and does not resorb over time. Dural substitutes comprising collagen have been also been explored as described in U.S. Pat. No. 5,997,895 (Narotam et al.). Integra Lifesciences Corporations (Plainsboro, N.J.) distributes a product known as DuraGen. The product is manufactured from bovine achilles tendon and is a pliable porous sheet. Although the material is resorbable and biocompatible, the integrity of the material is not sufficient enough to withstand suturing to the wound site.
The present invention overcomes these suturing and other difficulties of the materials currently available and provides a structure capable of being adapted to a wide variety of surgical applications.
Other applications for the implantable prosthesis of this invention, in the form of a surgical mesh, include pelvic floor disorders such uterine and vaginal vault prolapse. These disorders typically result from weakness or damage to normal pelvic support systems. The most common etiologies include childbearing, removal of the uterus, connective tissue defects, prolonged heavy physical labor and postmenopausal atrophy. Many patients suffering from vaginal vault prolapse also require a surgical procedure to correct stress urinary incontinence that is either symptomatic or latent.
Another embodiment of the present invention is directed to devices useful as prosthetic menisci, and in vivo or ex vivo scaffolds for regeneration of meniscal tissue.
The medial and lateral menisci are a pair of cartilaginous structures in the knee joint which together act as a stabilizer, a force distributor, and a lubricant in the area of contact between the tibia and femur. Damaged or degraded menisci can cause stress concentrations in the knee thereby creating abnormal joint mechanics and leading to premature development of arthritic changes.
In the prior art, treatment of injured or diseased menisci has generally been both by surgical repair and by tissue removal (i.e., excision). With excision, regeneration of meniscal tissue may not always occur. Allografting or meniscal transplantation is another method of replacement, which has been previously tried.
This approach has been only partially successful over the long term due to the host's immunologic response to the graft and to failures in cryopreservation and other processes. Alternately, menisci have been replaced with permanent artificial prostheses such as Teflon and polyurethane. Such prostheses have been selected to be inert, biocompatible, and structurally sound to withstand the high loads which are encountered in the knee joint. Typically, these permanent implants do little to encourage the regeneration of the damaged host tissue. Therefore, what is needed is an improved prosthetic meniscus composed of biocompatible materials, which are biocompatible, compliant, durable, and suitable to acts as a temporary scaffold for meniscal fibrocartilage infiltration and regeneration of the host tissue.
In U.S. Pat. No. 5,184,574 granted to Stone and U.S. Pat. No. 6,042,610 granted to Li, there is disclosed a meniscus replacement material, manufactured by shape molding collagen fibers within a mold via application of low pressure by a piston prior to or after drying. Stone requires the step of applying freezing cycles to the material. The fibrous materials achieve densities of 0.07-0.5 g/cc. Hydrated fibers at these density range from a free flowing liquid slurry to a loose dough-like material unable to maintain a shape. Freezing and possibly lyophilizing of the material is necessary to remove it from the mold and cross-linking solutions are applied to it while still in the frozen or lyophilized state so that it does not warp. Fiber orientation may be obtained by applying a rotating force to the piston in order to form a circumferential orientation. However, this orientation occurs only in areas directly in contact with the rotating piston. What is necessary is a fibrous construct with sufficient integrity to be handled without the necessity of freezing and/or lyophilizing and that can be implanted without the requirement of cross-linking, if desired. Additionally, this construct lacks any consistency throughout the thickness of its structure, being able to create oriented fibers only at the periphery.
Another embodiment of the present invention is directed to devices useful as prosthetic ligament, and in vivo or ex vivo scaffold for regeneration of ligament tissue and to methods for their fabrication.
The anterior cruciate ligament (ACL) of the knee functions to resist anterior displacement of the tibia from the femur during flexure. The ACL also resists hyperextension and serves to stabilize the fully extended knee during internal and external tibial rotation. Partial or complete tears of the ACL are common. The preferred treatment of the torn ACL is ligament reconstruction, using a bone-ligament-bone autograft (e.g., from the patient's patellar tendon or hamstring tendon). Cruciate ligament reconstruction generally provides immediate stability and a potential for immediate vigorous rehabilitation. However, ACL reconstruction is not ideal; the placement of intraarticular hardware is required for ligament fixation; anterior knee pain frequently occurs, and there is an increased risk of degenerative arthritis with intraarticular ACL reconstruction. Another method of treating ACL injuries involves suturing the torn structure back into place.
This repair method has the potential advantages of a limited arthroscopic approach and minimal disruption of normal anatomy. A disadvantage of this type of repair is that there is generally not a high success rate for regeneration of the damaged tissues due to the lack of a scaffold or other cellular inductive implant.
Another embodiment of the present invention relates to devices useful as a prosthetic intervertebral disc. The intervertebral disc plays an important role in stabilizing the spine and distributing the forces between the vertebral bodies. In the case of a damaged, degenerated, or removed disc, the intervertebral space collapses over time and leads to abnormal joint mechanics and premature development of arthritis.
In the prior art, discs have been replaced with prostheses composed of artificial materials. The use of purely artificial materials in the spine minimizes the possibility of an immunological response. Such materials must withstand high and repeated loads seen by the spinal vertebral joints, early attempts focused upon metallic disc implants. These efforts met with failure due to continued collapse of the disc space and or erosion of the metal prosthesis into the adjacent bone.